The metabolic interaction of toluene and ethanol was studied in male rabbits having received ethanol (26.0 mmol/kg PO), toluene (5.4 mmol/kg PO) or both. Compared with ethanol alone, toluene given 2 h after ethanol caused a significantly higher and more prolonged concentration of blood alcohol. A similar trend of blood alcohol was observed at the later stage with toluene given prior to ethanol. On the other hand, with simultaneous doses of the two substances, the blood toluene concentration was higher for the first 15-30 min than the ethanol control and the urinary excretion of hippuric acid, a main metabolite of toluene, was markedly decreased for the first 2 h. The blood ethanol in this group, on the contrary, was reduced until 1 h after administration. These results indicate that toluene and ethanol act reciprocally as competitive inhibitors in their metabolism after single administrations.